Event-Free Survival in Patients with Early HER2-Positive Breast Cancer with a Pathological Complete Response after HER2-Targeted Therapy: A Pooled Analysis

SIMPLE SUMMARY: The current standard of care for patients with HER2-positive early breast cancer who have a pathological complete response after neoadjuvant HER2-targeted therapy plus chemotherapy is continuation of HER2-targeted therapy in the adjuvant setting. However, it is not clear how long-term outcomes differ by the HER2-targeted regimen received in each setting. To investigate this question, we pooled patient-level data (n = 1763) from neoadjuvant studies of trastuzumab and pertuzumab to evaluate outcomes with respect to single versus dual HER2 targeting in the neoadjuvant and adjuvant settings. Patients treated with dual HER2-targeted therapy in both the neoadjuvant and adjuvant settings had the highest 4-year event-free survival rates, suggesting that this treatment approach may provide the most benefit for patients with HER2-positive early breast cancer. ABSTRACT: The standard-of-care for patients with pathological complete response (pCR) after neoadjuvant human epidermal growth factor receptor 2 (HER2)-targeted therapy plus chemotherapy is continuation of HER2-targeted therapy in the adjuvant setting. Our objective was to evaluate risk of recurrence or death in these patients and determine if outcomes differed by the HER2-targeted regimen received in each setting. We analyzed patient-level data from five randomized trials evaluating trastuzumab, pertuzumab, or both as part of systemic neoadjuvant and adjuvant therapy for HER2-positive early breast cancer, and assessed event-free survival (EFS) in 1763 patients. Patients with pCR had decreased risk of an EFS event versus those with residual disease (unadjusted hazard ratio [HR] = 0.35; 95% confidence interval [CI]: 0.27–0.46). Regardless of pCR status, after adjusting for baseline factors, reduction in EFS event risk was greater in patients administered pertuzumab/trastuzumab in both settings versus those administered only trastuzumab in both settings (HR = 0.36; 95% CI: 0.26–0.49), or pertuzumab/trastuzumab in the neoadjuvant setting and only trastuzumab in the adjuvant setting (HR = 0.67; 95% CI: 0.47–0.96). Patients with pCR had longer EFS than those with residual disease. Patients treated with pertuzumab/trastuzumab in both the neoadjuvant and adjuvant settings had the lowest risk of breast cancer recurrence.